(+)‐Sesamin‐oxidising CYP92B14 shapes specialised lignan metabolism in sesame

Abstract

Sesamum spp. (sesame) are known to accumulate a variety of lignans in a lineage-specific manner. In cultivated sesame (Sesamum indicum), (+)-sesamin, (+)-sesamolin and (+)-sesaminol triglucoside are the three major lignans found richly in the seeds. A recent study demonstrated that SiCYP92B14 is a pivotal enzyme that allocates the substrate (+)-sesamin to two products, (+)-sesamolin and (+)-sesaminol, through multiple reaction schemes including oxidative rearrangement of a-oxy-substituted aryl groups (ORA). In contrast, it remains unclear whether (+)-sesamin in wild sesame undergoes oxidation reactions as in S. indicum and how, if at all, the ratio of the co-products is tailored at the molecular level. Here, we functionally characterised SrCYP92B14 as a SiCYP92B14 orthologue from a wild sesame, Sesamum radiatum, in which we revealed accumulation of the (+)-sesaminol derivatives (+)-sesangolin and its novel structural isomer (+)-7´episesantalin. Intriguingly, SrCYP92B14 predominantly produced (+)-sesaminol either through ORA or direct oxidation on the aromatic ring, while a relatively low but detectable level of (+)-sesamolin was produced. Amino acid substitution analysis suggested that residues in the putative distal helix and the neighbouring heme propionate of CYP92B14 affect the ratios of its co-products. These data collectively show that the bimodal oxidation mechanism of (+)-sesamin might be widespread across Sesamum spp., and that CYP92B14 is likely to be a key enzyme in shaping the ratio of (+)-sesaminol-and (+)-sesamolin-derived lignans from the biochemical and evolutionary perspectives.

Tandem UGT71B5s Catalyze Lignan Glycosylation in Isatis indigotica With Substrates Promiscuity

“…In this study, we found that the pinoresinol in I. indigotica is not only catalyzed by PLR to produce lariciresinol and secoisolariciresinol ( Xiao et al, 2015 ; Zhang et al, 2016 ), but also accumulates in the form of its glucosides ( Figure 1 ; Supplementary Table S5 ), which may be influenced by functional differentiation of UGT71B5s. In addition, some categories of lignans are not produced in I. indigotica , such as sesaminol and podophyllotoxin, which is due to the functional diversity of gene families involved in the lignan biosynthesis network, including CYPs ( Murata et al, 2017 ; Harada et al, 2020 ), OMTs ( Lau and Sattely, 2015 ), and UGTs ( Ono et al, 2020 ). Studying the activity, diversity, and evolution of these families will help to reveal mechanisms for the diversity of lignans in plants.…”

Lignans of Sesame (Sesamum indicum L.): A Comprehensive Review

“…Furofuran lignan (+)-sesangolin was purified from S. angolense in a search for new synergists because seed oil of S. angolense possessed unusually high synergistic activity with pyrethrum [ 91 ]. Sesangolin was later reported from S. angustifolium [ 87 ], S. alatum [ 88 ], and S. radiaum [ 92 ]. Both alatumin [ 89 ] and episesalatin [ 90 ] were found in S. alatum .…”

“…Both alatumin [ 89 ] and episesalatin [ 90 ] were found in S. alatum . The most recent contribution to the diversity of sesame lignans is (+)-7′-episesantalin, which was purified from S. radiatum [ 92 ].…”

“…Thus, papers published between 1994 and 2010 might have spread the wrong data; an example is an industrial compendium on oils [ 235 ]. Recently, a Suntory Foundation for Life Sciences and their collaborators in Japan [ 92 ] re-investigated the content of lignans in seeds of S. radiatum , confirmed sesamin and sesamolin, and discovered the sesangolin isomer (+)-7′-episesantalin. Likewise, they re-discovered the presence of (+)-sesangolin, apparently not aware of the publication by Su Rho Ruy and coworkers from 1993 in Korean language, in which sesangolin was reported from S. radiatum for the first time [ 88 ].…”

“…The sequential conversion from pinoresinol to secoisolariciresinol and to matairesinol is proposed in sesame based on Forsythia intermedia biosynthetic pathway [ 244 , 245 ]. The convertion of sesamin to 7′-episesantalin has been recently proposed to occur in S. radiatum [ 92 ].…”